| First Author | Kirshenbaum GS | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 44 | Pages | 18144-9 |
| PubMed ID | 22025725 | Mgi Jnum | J:180250 |
| Mgi Id | MGI:5305901 | Doi | 10.1073/pnas.1108416108 |
| Citation | Kirshenbaum GS, et al. (2011) Mania-like behavior induced by genetic dysfunction of the neuron-specific Na+,K+-ATPase alpha3 sodium pump. Proc Natl Acad Sci U S A 108(44):18144-9 |
| abstractText | Bipolar disorder is a debilitating psychopathology with unknown etiology. Accumulating evidence suggests the possible involvement of Na(+),K(+)-ATPase dysfunction in the pathophysiology of bipolar disorder. Here we show that Myshkin mice carrying an inactivating mutation in the neuron-specific Na(+),K(+)-ATPase alpha3 subunit display a behavioral profile remarkably similar to bipolar patients in the manic state. Myshkin mice show increased Ca(2+) signaling in cultured cortical neurons and phospho-activation of extracellular signal regulated kinase (ERK) and Akt in the hippocampus. The mood-stabilizing drugs lithium and valproic acid, specific ERK inhibitor SL327, rostafuroxin, and transgenic expression of a functional Na(+),K(+)-ATPase alpha3 protein rescue the mania-like phenotype of Myshkin mice. These findings establish Myshkin mice as a unique model of mania, reveal an important role for Na(+),K(+)-ATPase alpha3 in the control of mania-like behavior, and identify Na(+),K(+)-ATPase alpha3, its physiological regulators and downstream signal transduction pathways as putative targets for the design of new antimanic therapies. |
